Antibody-Based Protection of von Willebrand Factor Degradation.

Recently, Bartoli et al. (1) reported on the use of doxycycline to reduce ADAMTS-13-mediated von Willebrand factor degradation during supraphysiological shear stress. We have read their article with interest, noticing reference in their discussion to one of our recent publications that appeared in Thrombosis and Haemostasis (2). However, we would like to correct some significant misinterpretations of our data as cited by the investigators. Indeed, our antibody is referred to as a monoclonal antihuman ADAMTS-13 antibody. This is incorrect. In fact, we have reported on the discovery and characterization of a monoclonal antihuman von Willebrand factor antibody, designated Mab508. This is not only clearly written in the abstract, but our article also describes in detail the epitope within von Willebrand factor that is recognized by this antibody. Describing our antibody as being antihuman ADAMTS-13 is therefore an important oversight. Second, the investigators suggest that our antibody blocks ADAMTS-13 activity by 83% and that such widespread inhibition may inadvertently provoke a hypercoagulable, thrombotic thrombocytopenic purpura–like state and thrombosis. The investigators seem to confuse 2 types of experiments reported in our article. First, we clearly show that the anti–von Willebrand factor antibody blocks binding and degradation of von Willebrand factor by ADAMTS-13 by a maximum of 50%. The figure 83% actually refers to the inhibition of the high– molecular weight multimers, not of von Willebrand factor as a whole. This is an essential difference, as it actually prevents (rather than induces) Mab508 from provoking the occurrence of ultralarge von Willebrand factor multimers that could potentially induce thrombotic thrombocytopenic purpura–like symptoms. This specificity is an important strength of our antibody, particularly when compared with the nonspecific inhibition of ADAMTS-13 and other proteases that is achieved when using doxycycline. We hope that this letter clarifies the scope of our article (identification of an anti–Von Willebrand factor antibody that partially interferes with ADAMTS13-mediated degradation).